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Mechanisms underlying iBALT generation, particularly during chronic CS exposure, remain to be defined. Oxysterol metabolism of cholesterol is crucial to immune cell localization in secondary lymphoid tissue. Here, we demonstrate that oxysterols also critically regulate iBALT generation and the immune pathogenesis of COPD. In both COPD patients and cigarette smoke (CS)\u2010exposed mice, we identified significantly upregulated CH25H and CYP7B1 expression in airway epithelial cells, regulating CS\u2010induced B\u2010cell migration and iBALT formation. Mice deficient in CH25H or the oxysterol receptor EBI2 exhibited decreased iBALT and subsequent CS\u2010induced emphysema. Further, inhibition of the oxysterol pathway using clotrimazole resolved iBALT formation and attenuated CS\u2010induced emphysema\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    therapeutically. Collectively, our studies are the first to mechanistically interrogate oxysterol\u2010dependent iBALT formation in the pathogenesis of COPD, and identify a novel therapeutic target for the treatment of COPD and potentially other diseases driven by the generation of tertiary lymphoid organs.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201708349","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T06:15:12Z","timestamp":1524118512000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Cholesterol metabolism promotes B\u2010cell positioning during immune pathogenesis of chronic obstructive pulmonary disease"],"prefix":"10.1038","volume":"10","author":[{"given":"Jie","family":"Jia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-6612","authenticated-orcid":false,"given":"Thomas M","family":"Conlon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rim SJ","family":"Sarker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demet","family":"Ta\u015fdemir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia F","family":"Smirnova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barkha","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stijn E","family":"Verleden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gizem","family":"G\u00fcne\u015f","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"Prehn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Heinzelmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutta","family":"Lintelmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Irmler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Pfeiffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schloter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hrab\u00e9 de Angelis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Beckers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy","family":"Adamski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hasan","family":"Bayram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-0360","authenticated-orcid":false,"given":"Oliver","family":"Eickelberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1969-480X","authenticated-orcid":false,"given":"Ali \u00d6nder","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,4,19]]},"reference":[{"key":"BFEMMM201708349_CR1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1084\/jem.20160675","volume":"214","author":"HA Baarsma","year":"2017","unstructured":"Baarsma HA, Skronska\u2010Wasek W, Mutze K, Ciolek F, Wagner DE, John\u2010Schuster G, Heinzelmann K, Gunther A, Bracke KR, Dagouassat M et\u00a0al (2017) Noncanonical WNT\u20105A signaling impairs endogenous lung repair in COPD. 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